Magnetic Susceptibility-Based Protein Detection Using Magnetic Levitation

Abstract

Magnetic levitation, which is a magnetic phenomenon of levitating particles suspended in a paramagnetic liquid under a nonuniform magnetic field, is a powerful tool for determining densities and magnetic properties of micro- and nanoparticles. The levitation height of particles in the magnetic field depends on the magnetic susceptibility and density difference between the object and the surrounding liquid. Here, we developed a magnetic susceptibility-based protein detection scheme in a low-cost and miniaturized magnetic levitation setup consisting of two opposing magnets to create a gradient of a magnetic field, a glass capillary channel to retain the sample, and two side mirrors to monitor inside the channel. The method includes the use of polymeric microspheres as mobile assay surfaces and magnetic nanoparticles as labels. The assay was realized by capturing the target protein to the polymer microspheres. Then, magnetic nanoparticles were attached onto the resulting microsphere–protein complex, creating a significant difference in the magnetic properties of polymer microspheres compared to those without protein. The change in the magnetic properties caused a change in the levitation height of the microspheres. The levitation heights and their distribution were then correlated to the amount of target proteins. The method enabled a detection limit of ∼110 fg/mL biotinylated bovine serum albumin in serum. With the sandwich immunoassay developed for mouse immunoglobulin G, detection limits of 1.5 ng/mL and >10 ng/mL were achieved in buffer and serum, respectively. This approach sensed the minute changes in the volume magnetic susceptibility of the microspheres with a resolution of 4.2 × 10–8 per 1 μm levitation height change.

A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers

“…Several studies reported the biochemical sample handling using microfluidic and magnetic beads to capture protein markers [9,10]. In addition, one of the notable reports proposed a magnetic susceptibility-based protein detection using magnetic levitation [11].…”

“…Another popular method to avoid the requirement of an electric pump in the microfluidic system is the capillary-driven chip [11,[14][15][16]. The capillary attraction can be driven by porous or cellulose materials, such as thread, woven fabrics, paper [17][18][19][20][21][22], and cellulose sponges [16,23,24].…”

Biomedical Applications of Magnetic Levitation

“…[48] For protein detection, a magnetic susceptibility-based MagLev platform was integrated with an inverted microscope for imaging. [37] The principle of magnetic susceptibility is based on labeling the protein with magnetic nanoparticles (MNPs), thus changing the beads' magnetic susceptibility. Generally, polymer microspheres levitate in the midpoint between the two magnets because they have no magnetic susceptibility.…”

“…The magnetic susceptibility difference between the object and the medium, under a magnetic field, is exploited to suspend particles, [ 37 ] which is either based on positive or negative magnetophoresis. In positive magnetophoresis, paramagnetic materials are manipulated in a diamagnetic medium.…”

“…MagLev devices are portable, [ 35 ] low cost, [ 36,37 ] label‐free, [ 38–41 ] easy to use, [ 42 ] and accurate. [ 9,43 ] MagLev has applications in measuring the density of polymers and characterizing polymer composition, [ 4,9 ] and analysis of crystal polymorphs, [ 3 ] biopolymers, [ 9 ] chemicals, biochemical particles, [ 1 ] nutrition content of food products (e.g., dairy), [ 44 ] and proteins.…”